Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

OBJECTIVE: To explore the clinical effect of personalized puncture planning before surgery using Picture Archiving and Communication System (PACS) in the treatment of osteoporotic vertebral compression fractures in the elderly. METHODS: A total of 69 elderly patients with osteoporotic vertebral compression fractures treated by percutaneous vertebroplasty from January 2020 20 to December 2021 with more than 1 year of follow-up were analyzed retrospectively. Thirty-four patients were individualized for preoperative planning with PACS software (observation group), including 8 males and 26 females, with a mean age of (73.30±7.96) years old;and 35 patients were treated with conventional treatment (control group), including 7 males and 28 females, with a mean age of (77.30±7.84) years old. The operation time, the amount of cement injection, cement leakage rate, bone watertight diffusion and refracture within 1 year between two groups were observed and compared. The Cobb's angle, low back pain visual analogue scale(VAS) and the modified Oswsetry disability indexes(ODI) before surgery and 1 day, 1 year after surgery were compared between two groups. RESULTS: Both groups successfully completed the operation without serious surgical complications, 2 refractures occurred in the control group. The operation time in the observation group was(41.9±11.9) min, which was less than that in the control group (52.7±13.6) min (P<0.05). There was no significant difference in the cement injection volume between two groups (P>0.05). Two cases of cement leakage in the observation group was less than 8 in the control group (P<0.05). The bone cement distribution index of two groups had significant difference(P<0.05). There were no significant differences between two groups in Cobb's angle of the injured vertebras and ODI before and 1 day after surgery(P>0.05), however, the comparative differences were statistically significant at 1 year after surgery(P<0.05). There was no significant difference in the VAS between two groups at each time period(P>0.05). CONCLUSION Using the PACS software to plan personalized puncture scheme can reduce the operation time, reduce the cement leakage rate, improve the diffusion of bone cement and longer maintain the postoperative form of vertebral body and the functional state of patients' lumbar back.
Humans ; Male ; Female ; Aged ; Vertebroplasty/methods* ; Fractures, Compression/diagnostic imaging* ; Spinal Fractures/diagnostic imaging* ; Osteoporotic Fractures/diagnostic imaging* ; Aged, 80 and over ; Retrospective Studies ; Radiology Information Systems

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

BACKGROUND: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence. METHOD: In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly. RESULTS: A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM_2.5, PM₁₀/CO, and O₃ /SO₂/NO₂, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m³ for PM_2.5, 57.93 µg/m³ for PM₁₀, 56 µg/m³ for O₃, below 643.6 µg/m³ for CO, and within 33 and 48 µg/m³ for NO₂. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds. CONCLUSION Non-linear associations were found between air pollutants and MASLD prevalence. PM_2.5, PM₁₀, O₃, CO, and NO₂ exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.
Humans ; Nitrogen Dioxide ; Cross-Sectional Studies ; Air Pollution/analysis* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Liver Diseases ; Environmental Exposure/analysis*

Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme of the pentose phosphate pathway, which regulates the production of nicotinamide adenine dinucleotide phosphate (NADPH) in cells, and plays an important role in redox reactions. In addition, NADPH is necessary for biosynthesis reactions and is an essential hydrogen donor in the biosynthesis of cholesterol, fatty acids, and sex hormones. NADPH also plays an important role in maintaining intracellular redox homeostasis, converting intracellular oxidized glutathione into reduced glutathione (GSH), which is the main intracellular antioxidant. Therefore, G6PD plays an important role in maintaining intracellular redox homeostasis. Studies have shown that the decrease in G6PD activity can lead to a breakdown of the redox balance in the cells and tends to the oxidation state, which not only leads to dysregulation of cell growth and signaling, but also makes the host more susceptible to viruses. Previous studies have focused on the molecular characteristics of G6PD, anemia caused by G6PD deficiency, and the relationship between malignant tumors and G6PD. In recent years, more attentions have been paid to the importance of G6PD at the cellular level, development, and disease progression. To explore the effects of G6PD on viral life cycle, the relationship between G6PD and viral infections, including the clinical symptoms and virus-host interactions of hepatitis B virus (HBV), human papilloma virus (HPV), hepatitis E virus (HEV), influenza virus and dengue fever virus (DENV) will be reviewed, which will benefit the antiviral drugs development. Many studies had proved that patients with deficient G6PD are more susceptible to HBV infection. It has been reported that HBV infection activates the glycolytic pathway, promotes pentose phosphate pathway, and accelerates citric acid cycle to enhance nucleotide and fat biosynthesis, thereby promoting viral replication. During HPV infection, miR-206 up-regulates the expression of G6PD to facilitate viral replication. Thus, G6PD may be a new target for anti-cervical cancer therapy. It was reported that patients with G6PD deficiency are more susceptible to HEV infection, and more serious HEV infection-associated diseases are developed. However, the mechanism of why and how the deficiency of G6PD affect HEV infection is still unclear. The oxidative stress caused by G6PD deficiency provides a suitable environment for influenza virus replication. Furthermore, patients with G6PD deficiency are more susceptible to SARS-CoV-2 infection and lead to more severe clinical symptoms with a higher risk of thrombosis and hemolysis than general population. There is a correlation between DENV infection and G6PD deficiency, which increase the risk of hemolysis, however, the pathogenesis is still unknown. The deficiency of G6PD promotes HCoV 229E infection, possibly because the NF-κB signal pathway is suppressed when G6PD deficiency, which results in decreased innate antiviral immune, and increased susceptibility to HCoV 229E, finally leads to increased viral replication. Thus, the deficiency of G6PD play an important role during viruses’ infection, especially the susceptibility. More studies should be performed on the relicationship between G6PD deficiency and specific viral susceptibility, and more attentions shoud be paid to G6PD deficient patients, which will benefit the treatment of viral infection and the development of antiviral drugs.